Saturday, October 31, 2015

Jeffrey Sank always knew when he was going to have an attack: Its onset was signaled by the same kind of uneasy, "uh-oh" feeling that portends an impending cold.

But Sank's problem wasn't in his head — it was in his gut. And when he felt the initial abdominal pangs, he knew that he had about 12 hours before he was miserable, or at worst incapacitated, for the next day or two.

"It almost felt like I'd done 1,000 sit-ups or been punched in the gut 100 times," said the digital media specialist, 43, who lives in the District. At first the attacks were intermittent. But after several months the pain, centered in the right upper quadrant where the liver and gallbladder are located, increased in severity and frequency.

For nearly a year, Sank, with the help of his stepmother, a physician, struggled to determine the reason for his pain. He saw multiple doctors, including two gastroenterologists, a kidney specialist and an infectious-disease physician. He underwent workups for reflux disease, a liver disorder, an intestinal blockage and malaria. One doctor suspected he might be faking.

Sank's problem turned out to be none of those things. His diagnosis was partly the result of serendipity: The second gastroenterologist he consulted was familiar with the malady, which is common in other parts of the world but not the United States. To complicate matters, Sank's case did not fit the standard diagnostic criteria.

"It's in the differential [a list of possible disorders suggested by symptoms], but since we never really see it, you don't necessarily think of it," said Montgomery County gastroenterologist William Steinberg. Luckily, something Steinberg had seen two decades earlier on a medical trip to the Middle East resonated when an increasingly desperate Sank consulted him in April 2010.

The first time he suffered stomach pain in June 2009, Sank assumed he had food poisoning. "I really didn't think much about it," he recalled.

When it kept recurring, he consulted his stepmother, Catherine Shaer, a retired pediatrician, for advice. Sank was otherwise healthy, and Shaer agreed that he should see a gastroenterologist.

At his initial appointment in October 2009, the gastroenterologist told Sank he suspected his pain was the result of gallstonesand ordered a sonogram.

The test was memorable: Sank said that during the procedure the technician began acting strangely and then summoned a radiologist. In a somber voice, Sank recalled, the radiologist "told me that there was a huge lesion on my liver and they were going to send me immediately for a CT scan."

The radiologist then told him, Sank recalled, "there was something very serious going on here and that I needed to prepare myself and my family for what I had to deal with." Sank also remembers the specialist saying that his "door was always open."

"I thought I had liver cancer and was going to die," Sank remembered. At the time, his first child was only a few months old.

While waiting for the CT scan, Sank telephoned his stepmother and a friend who is an oncologist. Both told him that they were sure that the growth on his liver, the size of a large strawberry, would turn out to be a benign hemangioma. He had no cancer symptoms, and such tumors are common. A few hours later, Sank, hugely relieved, learned they were right. He didn't have cancer. Nor did he have gallstones. "We were back to square one," he recalled.

Thursday, October 22, 2015

Chronic pain affects approximately 100 million Americans and exacts large economic, social and personal costs. It is a major public health challenge that needs to be addressed at multiple levels including the generation of new scientific knowledge that will enhance our understanding of these conditions. Current research efforts in chronic pain conditions have focused on single disorders or types of pain such as neuropathic and inflammatory pain. These research efforts have generated a substantial body of information advancing our discovery and understanding of the underlying mechanisms of pain onset and development, the transition from acute to chronic pain, and promising therapeutic targets for treating acute and chronic pain. Over the past twenty years sporadic reports have documented the presence of more than one chronic pain condition in subjects with pain. Studies have identified overlap between a number of chronic pain conditions, including temporomandibular joint disorder (TMD), fibromyalgia (FM), vulvodynia, functional gastrointestinal disorders such as irritable bowel syndrome (IBS), migraine, and urologic chronic pelvic pain syndromes (UCPPS). These results suggest that chronic pain conditions may not be localized conditions, but may share symptoms and mechanisms that involve a general central nervous system dysfunction as well as disorder-specific symptoms. More recent evidence is supportive of the idea that chronic pain conditions are complex disorders consistent with a biopsychosocial model of pain, and exhibit substantial overlap. Therefore, this may be an opportune time to encourage research efforts that focus, not on single pain conditions, but on subjects with multiple chronic pain disorders.

Chronic pain conditions represent a complex set of painful disorders that lack a firm mechanistic understanding, and are in need of hypothesis-driven research efforts. A new focus on overlapping pain conditions is warranted to develop therapies to prevent and treat these overlapping disorders and to develop approaches to better manage pain that can be disabling. A workshop sponsored by the NIH Pain Consortium was held in the summer of 2012 titled "A Workshop on Chronic Overlapping Pain Conditions". It brought together researchers with expertise in various pain conditions and other relevant expertise to discuss these conditions and to develop a forward-thinking research agenda. The workshop focused on our current understanding of chronic overlapping pain conditions, their etiology, risk factors, mechanisms of disease, outcome measures, and diagnosis. Topics of discussion included epidemiology of chronic overlapping pain conditions, risk factors and mechanisms of disease, leveraging of current data sets, and new scientific approaches incorporating systems biology. The recommendations derived from this workshop have, in part, informed the development of this FOA.

The grants in the Federal pain research portfolio were classified using a multi-tiered system. In Tier 1, grants were designated as basic, translational, or clinical. Grants then were coded into 29 scientific topic categories (Tier 2). Following this classification, the Tier 2 categories were organized into 9 overarching themes based on similarity of topic.

The Patient Protection and Affordable Care Act (PPACA) includes a number of provisions designed to advance pain research, care, and education, including the creation of the Interagency Pain Research Coordinating Committee (IPRCC) by the Department of Health and Human Services (HHS). On behalf of HHS, the NIH established the IPRCC to coordinate all pain research efforts within HHS and across other Federal Agencies. The Committee is composed of seven Federal members and twelve non-Federal members, six drawn from the scientific and medical communities and six members of the public and stakeholder groups. The Department of Health and Human Services Secretary will review the necessity of the Committee at least once every 2 years.

As specified in Section 4305(b) of the Public Law 111-148 ("Affordable Care Act (ACA)") the Committee has been asked to:

Develop a summary of advances in pain care research supported or conducted by the Federal agencies relevant to the diagnosis, prevention, and treatment of pain and diseases and disorders associated with pain

Identify critical gaps in basic and clinical research on the symptoms and causes of pain

Make recommendations to ensure that the activities of the National Institutes of Health and other Federal agencies are free of unnecessary duplication of effort

Make recommendations on how best to disseminate information on pain care

Make recommendations on how to expand partnerships between public entities and private entities to expand collaborative, cross-cutting research

Sunday, October 18, 2015

I rushed into the bedroom and watched my wife, Rachel, stumble from the bathroom, doubled over, hugging herself in pain.

"Something's wrong," she gasped.

This scared me. Rachel's not the type to sound the alarm over every pinch or twinge. She cut her finger badly once, when we lived in Iowa City, and joked all the way to Mercy Hospital as the rag wrapped around the wound reddened with her blood. Once, hobbled by a training injury in the days before a marathon, she limped across the finish line anyway.

So when I saw Rachel collapse on our bed, her hands grasping and ungrasping like an infant's, I called the ambulance. I gave the dispatcher our address, then helped my wife to the bathroom to vomit.

I don't know how long it took for the ambulance to reach us that Wednesday morning. Pain and panic have a way of distorting time, ballooning it, then compressing it again. But when we heard the sirens wailing somewhere far away, my whole body flooded with relief.

I didn't know our wait was just beginning.

I buzzed the EMTs into our apartment. We answered their questions: When did the pain start? That morning. Where was it on a scale of one to 10, with 10 being worst?

"Eleven," Rachel croaked.

As we loaded into the ambulance, here's what we didn't know: Rachel had an ovarian cyst, a fairly common thing. But it had grown, undetected, until it was so large that it finally weighed her ovary down, twisting the fallopian tube like you'd wring out a sponge. This is called ovarian torsion, and it creates the kind of organ-failure pain few people experience and live to tell about.

"Ovarian torsion represents a true surgical emergency," says an article in the medical journal Case Reports in Emergency Medicine. "High clinical suspicion is important. … Ramifications include ovarian loss, intra-abdominal infection, sepsis, and even death." The best chance of salvaging a torsed ovary is surgery within eight hours of when the pain starts.

There is nothing like witnessing a loved one in deadly agony. Your muscles swell with the blood they need to fight or run. I felt like I could bend iron, tear nylon, through the 10-minute ambulance ride and as we entered the windowless basement hallways of the hospital.

And there we stopped. The intake line was long—a row of cots stretched down the darkened hall. Someone wheeled a gurney out for Rachel. Shaking, she got herself between the sheets, lay down, and officially became a patient.

Monday, October 12, 2015

A new study shows that women — especially younger women — are less likely than men to find relief from pain with long-term opioid use.

The new study, published in the Journal of Women's Health, found that only one in five women reported low levels of pain and high levels of function with chronic opioid therapy.

In the study, researchers led by Linda LeResche, Sc.D., of the Department of Oral Medicine at the University of Washington School of Dentistry in Seattle, evaluated pain status among chronic opioid therapy users.

The researchers report that young and middle-aged women are at particularly high risk for unfavorable global pain status.

Additionally, young and middle-aged women face "unique risks" from opioid use, such as reduced fertility and potential effects of opioids used during pregnancy on the developing fetus, the researchers reported.

"Given the high rates of chronic opioid use in women, along with evidence of poor relief from pain and concerning risks, particularly in reproductive-aged women, we need more effective and safer options for managing pain in this population," noted Susan G. Kornstein, M.D., editor-in-chief of the Journal of Women's Health, executive director of the Virginia Commonwealth University Institute for Women's Health in Richmond, Virginia, and president of the Academy of Women's Health.

Friday, October 09, 2015

Most new painkiller drugs fail in clinical trials — but a growing placebo response may be to blame.

Drug companies have a problem: they are finding it ever harder to get painkillers through clinical trials. But this isn't necessarily because the drugs are getting worse. An extensive analysis of trial data1 has found that responses to sham treatments have become stronger over time, making it harder to prove a drug's advantage over placebo.

The change in reponse to placebo treatments for pain, discovered by researchers in Canada, holds true only for US clinical trials. "We were absolutely floored when we found out," says Jeffrey Mogil, who directs the pain-genetics lab at McGill University in Montreal and led the analysis. Simply being in a US trial and receiving sham treatment now seems to relieve pain almost as effectively as many promising new drugs. Mogil thinks that as US trials get longer, larger and more expensive, they may be enhancing participants' expectations of their effectiveness.

Stronger placebo responses have already been reported for trials of antidepressants and antipsychotics2, 3, triggering debate over whether growing placebo effects are seen in pain trials too. To find out, Mogil and his colleagues examined 84 clinical trials of drugs for the treatment of chronic neuropathic pain (pain which affects the nervous system) published between 1990 and 2013.

Based on patients' ratings of their pain, the effect of trialled drugs in relieving symptoms stayed the same over the 23-year period — but placebo responses rose. In 1996, patients in clinical trials reported that drugs relieved their pain by 27% more than did a placebo. But by 2013, that gap had slipped to just 9%. The phenomenon is driven by 35 US trials; among trials in Europe, Asia and elsewhere, there was no significant change in placebo reponses.The analysis is in press in the journal Pain1.

Only in America

This effect would explain why drug companies have trouble getting new painkillers through trials, notes neuroscientist Fabrizio Benedetti, who studies placebo responses at the University of Turin, Italy. Over the past ten years, he says, more than 90% of potential drugs for treatment of neuropathic and cancer pain have failed at advanced phases of clinical trials.

But the finding that placebo responses are rising only in the United States is the most surprising aspect of the latest analysis. One possible explanation is that direct-to-consumer advertising for drugs — allowed only in the United States and New Zealand — has increased people's expectations of the benefits of drugs, creating stronger placebo effects. But Mogil's results hint at another factor. "Our data suggest that the longer a trial is and the bigger a trial is, the bigger the placebo is going to be," he says.

Longer, bigger US trials probably cost more, and the glamour and gloss of their presentation might indirectly enhance patients' expectations, Mogil speculates. Some larger US trials also use contract research organizations that can employ nurses who are dedicated to the trial patients, he adds — giving patients a very different experience compared to those who take part in a small trial run by an academic lab, for instance, where research nurses may have many other responsibilities.

No pain, no gain?

Mogil's data also challenge one of the fundamental principles of placebo-controlled trials — that comparing a drug against placebo tells us how well a drug works. A basic principle of these trials is that drug and placebo effects are additive: our total response to any drug we take is equal to the placebo response plus the drug's biochemical effect. But Mogil found that although placebo responses have increased over time, drug responses haven't risen by the same amount.

That suggests placebo and drug responses may not always be strictly additive. This isn't entirely unexpected, Mogil argues, because both placebos and pharmaceutical painkillers tap into similar biological mechanisms — such as the release of endorphins in the brain. But if true, it suggests that growing placebo responses are masking real painkilling effects. "There are a lot of people in the pain field who believe the drugs that are failing clinical trials actually work, it's just that the trials can't show it," he says.

For companies trying to develop treatments, one remedy might be to compare new drugs against their best competitors instead of against placebo — or to go back to conducting smaller, shorter trials. Benedetti is not convinced, however. "I don't think that controlling the placebo response will increase the number of successful trials," he says. "What drug companies have to do is to find more effective drugs."

Mogil suggests it is also worth investigating the elements that generate the more powerful placebo response in US trials, and then incorporating those elements (such as the relationship between patient and nurse) into patient care. Ted Kaptchuk, director of placebo research at Harvard Medical School in Boston, Massachusetts, agrees. "If the major component of a drug in any particular condition is its placebo component, we need to develop non-pharmacological interventions as a first-line response," he says.

Tuesday, October 06, 2015

The World Congress on Pain provides a state-of-the-art overview of a wide range of topics in pain research and treatment. It offers networking opportunities with thousands of the world's leading experts who are eager to share their thoughts, research, and findings. Whether you are a trainee entering the field, a clinician interested in updating your knowledge, or a researcher announcing promising new results, you will discover new information in plenary sessions, refresher courses, topical workshops, and poster sessions that define the cutting edge of pain research and treatment.

Scheduled to launch in July 2016, PAIN Reports is an international, peer-reviewed, online-only journal focused on pain research and management. It is multidisciplinary in scope, covering subjects appealing to basic and applied researchers and practitioners worldwide. With a dedicated focus on publishing brief original reports, communications, and full-length articles, PAIN Reports will support IASP's mission to "...bring together scientists, clinicians, health-care providers, and policymakers to stimulate and support the study of pain and translate that knowledge into improved pain relief worldwide."

All content published within PAIN Reports is openly available online immediately upon publication. Open-access publishing provides unrestricted access via the Internet to peer-reviewed scholarly research. Authors retain copyright of their articles, with content licensed under several Creative Commons licenses. The journal is funded through Author Processing Charges (APCs), which are paid by authors, funders, institutions, or sponsors of accepted articles. Because open-access journals are freely available online, there are no subscriptions. Furthermore, there are no maximum limitations on the number of papers or pages that can be published in the journal.

PAIN Reports will encourage and consider direct submissions. The submission system for PAIN Reports may be linked to the submission system for PAIN, allowing authors of manuscripts not accepted in PAIN to indicate that they wish to transfer their manuscripts directly to PAIN Reports for consideration

At this meeting you experienced a multidisciplinary, stimulating, and educational lecture series led by an international panel of invited speakers. We also brought together scientists and clinicians from around the world to present poster abstracts on the most cutting edge pediatric pain research.

Monday, October 05, 2015

Consider this trade-off the next time you have a headache: Would you take a medicine that didn't just ease the pain but muffled your happiness too?

A recent study suggests that acetaminophen—found in Tylenol, Excedrin and a host of other medications—is an all-purpose damper, stifling a range of strong feelings. Throbbing pain, the sting of rejection, paralyzing indecision—along with euphoria and delight—all appear to be taken down a notch by the drug.

For most people, this over-the-counter palliative doesn't demand much thought: Take the right dose and the pain goes away. But it may not be that simple.

In 2010, the psychologists Naomi Eisenberger and Nathan DeWall discovered that a three-week course of acetaminophen soothed social pain, like feelings of exclusion or ridicule. The drug also assuaged the agony of indecision, Dr. DeWall found earlier this year.

Building on this research, a new study, published in June in the journal Psychological Science, shows that acetaminophen affects not just how we perceive physical and psychological pain but how the brain processes strong feelings in general. Though the study was small and limited to college students as subjects, the researchers designed it to meet the high standards of pharmaceutical testing and were able to replicate it.